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Researchers Home In On Obesity Gene And Offer Explanation For Overeating

03.11.2003

An international team of researchers has identified the role of a gene which may explain why some people overeat and become obese.

Their research, published today in Public Library of Science Biology, shows that the gene GAD2 has an appetite stimulating role, and that one form of the gene is strongly associated with obese people.

While the researchers recognise that obesity is a result of the interactions of many genes and environmental factors, this is one of the first genes to be strongly touted as a candidate ‘gene for obesity’.

GAD2, which sits on chromosome 10, acts by speeding up production of a neurotransmitter in the brain called GABA, or gamma-amino butyric acid. When GABA interacts with another molecule named neuropeptide Y in a specific area of the brain - the paraventricular nucleus of the hypothalamus - we are stimulated to eat.

The researchers behind this study believe that people who carry a more active form of the GAD2 gene build up a larger than normal quantity of GABA in the hypothalamus, and suggest that this over accumulation of GABA drives the stimulus to eat further than normal, and is thus a basis for explaining why obese people overeat.

Professor Philippe Froguel, senior author of the research, from Imperial College London, and Hammersmith Hospital, London, and who carried out the research while at the Institut Pasteur de Lille, France, said: “The discovery that this one gene plays a role in determining whether someone is likely to overeat could be crucial in understanding the continued rise in obesity rates around the world.

“Genetic factors alone can not explain the rapid rise in obesity rates, but they may provide clues to preventative and therapeutic approaches that will ease the health burden associated with obesity.

“Having identified this gene, it may be possible to develop a screening programme to identify those who may be at risk of becoming obese later in life, and take effective preventative measures.”

The team compared genome-wide scans of 576 obese and 646 normal weight adults in France, from which they identified two alternative forms, or alleles, of the GAD2 gene.

One form of the gene was found to be protective against obesity, while another increased the risk of obesity. The normal weight group of French adults had a higher frequency of the protective form of the GAD2 gene. Obesity is three to five times less prevalent in France than in the USA.

In addition to the genome-wide scans, the obese patients also completed an eating habits questionnaire, measuring dietary restraint, disinhibition and perceived hunger. The results showed that those carrying the GAD2 allele that increases the risk of obesity were significantly more likely to reveal an inability to control their food intake, and perceive high levels of hunger.

Authors of this research are based at Imperial College London, Hammersmith Hospital, London, the Institut Pasteur de Lille, France, the University of Washington, USA, Paul Brousse Hospital, and Paris VI University, France.

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